Many microplate assays important in drug research, molecular biology, and biotechnology involve the binding or uptake of radioisotopic or luminescent tracers to target macromolecules or whole cells to form labelled complexes. Examples of microplate assays include DNA and RNA hybridizations (e.g., dot blots), enzyme activity assays (e.g., reverse transcriptase and kinases), receptor binding assays, and cell proliferation assays. A common feature of all these assays is that a labelled complex must be separated from any excess tracer that does not react with the target macromolecules or whole cells during the binding process. This is typically done by capturing or immobilizing the labelled complex on a suitable filter medium and washing away the unreacted tracer. Once separated, the material captured on the filter medium is typically assayed by autoradiography, liquid scintillation counting (LSC), or luminometry. In some cases, the filter medium is used to specifically bind the assay components, while in other cases the filter medium is used as a filtration medium. Assay performance is highly dependent on the type of filter material used, where typical filter materials include glass fiber, nylon, nitrocellulose, phosphocellulose, or other suitable material. Even differences in the same type of filter materials made by different suppliers may be subtle enough to adversely affect assay performance.
One technique for assaying samples captured on a filter medium requires the individual samples to be cut from the filter medium and counted in individual scintillation vials using a liquid scintillation counter (LSC). A drawback of this technique is that the analysis and quantitation of bound samples immobilized on the filter medium requires time consuming sample preparation. In addition, this technique is expensive because the individual scintillation vials containing large volumes of scintillation fluid are discarded following use.
Another technique for assaying samples captured on a filter medium encloses the filter medium in a sample bag, treats the filter medium with scintillation liquid, and places the bag containing the treated filter medium into a scintillation counter. To reduce crosstalk between the samples on the filter medium during analysis, the filter medium itself is provided with a printed crosstalk reducing pattern. An example of such a technique is the 1205 Betaplate system manufactured by Wallac Oy of Turko, Finland. While this technique substantially reduces the amount of time for sample preparation and analysis, the technique generally requires a user to employ special non-standard filters available only from the manufacturer of the scintillation counter. The 1205 Betaplate system, for example, employs a non-standard 6.times.16 filter format rather than the standard 8.times.12 filter format. If the user wants the benefit of reduced time for sample preparation and analysis, the user is locked into the filter medium produced by a particular manufacturer. The user cannot employ the filter of his or her choice. Moreover, since the crosstalk reducing pattern is built into the filter medium itself and the filter medium is discarded following use, the crosstalk reducing pattern and its manufacturing cost are consumed with the discarded filter medium. Yet another drawback of this technique is that the analyzed product, i.e., a bag containing a treated filter medium, is not in the microplate format. Thus, the filter medium in this technique cannot be used in any applications requiring the microplate format. A related drawback is that various types of ancillary equipment used in assays, including washing, dispensing, and stacking equipment, are adapted to operate with the microplate format. Since the filter medium in this technique is not included in a device having the microplate format, the filter medium cannot be used with such ancillary equipment.
Accordingly, there exists a need for a microplate assembly and method which overcomes the above-noted drawbacks associated with existing techniques.